Interleukin-4 induces expression of the integrin α_vβ₃ via transactivation of the β₃ gene

Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin α_vβ₃ whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on α_vβ₃ expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing β₃ mRNA levels by a mechanism involving transactivation of the β₃ gene. Moreover, IL-4 augmented β₃ mRNA is mirrored by plasma membrane appearance of α_vβ₃. As IL-4 induces β₃ and not α_v mRNA, the β₃ chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced α_vβ₃ is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of BMMs with the cytokine enhances α_vβ₃-mediated binding to vitronectin 5-fold. Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests α_vβ₃ may play a role in the inflammatory response of macrophages.